A long-range comprehensive program is proposed for study of the structure, function, and genetic control of a series of inadequately characterized human plasma proteins, principally alpha-glycoproteins and beta-glycoproteins. Some have identified function and clinical significance and others not, but in no case is much known about their structure. Emphasis will be on determination of amino acid sequence, disulfide bonding pattern, localization and kind of carbohydrate groups, and the combining sites of ligands such as metal ions. Correlation of function and structure will be sought, and interrelationships with other plasma proteins will be investigated. Some correlations will be done in cooperation with other groups studying changes in plasma proteins in disease, their genetic polymorphism and variation, and possibly their three-dimensional structure. The first proteins selected for study are ceruloplasmin, a copper-containing protein with ferroxidase activity that is involved in copper metabolism, and Beta 2-glycoprotein I, a crystallizable protein of high carbohydrate content and of unknown function. Proteins for future study would be selected from among the antiproteases and a series of metal-binding alpha- and Beta-glycoproteins. The long range goals are to make a major contribution to knowledge about human plasma proteins, to integrate information gained from in vitro study with in vivo function, and to focus attention on the characterization, quantitation, and clinical significance of this group of proteins from human blood plasma. The methods to be used include amino acid and carbohydrate analysis, amino acid sequence analysis, immunochemical and physicochemical characterization, nuclear magnetic resonance spectroscopy, and other procedures for structural study of proteins and carbohydrates. BIBLIOGRAPHIC REFERENCES: Liu, Y-S.V. and Putnam, F.W., Federation Proc. 36 (in press) (1977) (Abs.), Clostripain specificity on human beta2-glycoprotein I. Putnam, F.W. (ed.), The Plasma Proteins: Structure, Function, and Genetic Control, 2nd Ed., Vol. III, Academic Press, New York, NY (1977), in press.